Stem cells are cells having the ability to divide to an unlimited extent and to differentiate under suitable circumstances and/or through suitable stimuli to form different types of cells. Stem cells have the potential to develop into cells with a characteristic shape and specialized functions.
Because of their different potential for differentiating into different cell types, a distinction has been made so far between embryonal stem cells and adult stem cells. It is the general consensus that the potency of stem cells decreases with their development from the fertilized egg cell to the embryonal stage to the adult organism. According to this property, the fertilized egg cell is referred to as totipotent, embryonal stem cells are referred to as pluripotent and adult stem cells are referred to as multipotent.
Totipotent cells are cells from which a complete organism can develop. In addition to the fertilized egg cell, these also include the cells of the early embryonal phase. Pluripotency is understood to refer to the fact that the embryonal stem cells which are typically obtained from the internal cell mass of disaggregated blastocytes are capable of differentiating into cells of all three germ layers—mesoderm, endoderm and ectoderm.
According to learned opinion so far, however, adult stem cells are only multipotent, i.e., they are capable of differentiation only to a lesser extent. Thus tissue-specific stem cells should be capable only of differentiation into cells of the same tissue type. In recent years, this view had to be corrected at least in part because investigations with adult stem cells obtained, for example, from bone marrow (WO 02/064748) or from regenerative tissue (WO 02/057430) have proven that under certain conditions, e.g., transplantation into a target tissue, culturing on a feeder cell layer and/or culturing in the presence of specific growth factors, differentiation of individual stem cells to form cell types of different germ layers is also achievable. However, these adult stem cells are still not equivalent to the embryonal stem cells with regard to self-renewal ability and differentiation potential. In particular the stability of these cell lines in long-term culturing is not ensured and the cells have a tendency to spontaneous differentiation and under some circumstances even to malignancy to develop tumor cells. Furthermore the rate of proliferation declines significantly with longer culturing.
Thus in view of the ethical objections with regard to embryonal stem cells, there is still a great deal of interest in new adult stem cells with the greatest possible differentiation potential and with properties equivalent to those of the embryonal stem cells.
Therefore the object of this invention is to provide new adult stem cells which no longer have any significant differences in their self-renewal ability and differentiation potential in comparison with embryonal stem cells and which can be referred to as actually pluripotent. One related object is to provide new and especially simple methods of isolation and culturing of adult pluripotent stem cells and differentiated cells derived thereof. Another related object is to provide new pharmaceutical compositions and methods of treatment of various disease states using pluripotent stem cells.
These objects are achieved according to this invention by providing isolated pluripotent adult stem cells which have been obtained from exocrine glandular tissue as well as the inventive methods of isolating and culturing these stem cells and differentiated cells derived therefrom and by providing pharmaceutical compositions and methods of treatment using the inventive stem cells and/or differentiated cells derived therefrom.